Differential Contribution of Pacemaker Properties to the Generation of Respiratory Rhythms during Normoxia and Hypoxia

• Published in: Neuron (Cambridge, Mass.) Vol. 43; no. 1; pp. 105 - 117
• Main Authors: Peña, Fernando, Parkis, Marjorie A, Tryba, Andrew K, Ramirez, Jan-Marino
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.07.2004; Elsevier Limited
• Subjects: Action Potentials - drug effects; Action Potentials - physiology; Animals; Biological Clocks - drug effects; Biological Clocks - physiology; Cadmium - pharmacology; Cell Membrane - drug effects; Cell Membrane - physiology; Female; Flufenamic Acid - pharmacology; GABA-A Receptor Antagonists; Hypoxia; Hypoxia, Brain - physiopathology; In Vitro Techniques; Lanthanum - pharmacology; Male; Mammalia; Medulla Oblongata - drug effects; Medulla Oblongata - physiology; Mice; Nerve Net - drug effects; Nerve Net - physiology; Neural networks; Neurons; Periodicity; Population; Receptors, GABA-A - metabolism; Receptors, Glycine - antagonists & inhibitors; Receptors, Glycine - metabolism; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - metabolism; Respiration - drug effects; Respiratory Center - drug effects; Respiratory Center - physiology; Rhythm; Riluzole - pharmacology; Sodium Channel Blockers - pharmacology; Sodium Channels - drug effects; Sodium Channels - physiology; Synaptic Transmission - drug effects; Synaptic Transmission - physiology
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2004.06.023

Pacemaker neurons have been described in most neural networks. However, whether such neurons are essential for generating an activity pattern in a given preparation remains mostly unknown. Here, we show that in the mammalian respiratory network two types of pacemaker neurons exist. Differential blockade of these neurons indicates that their relative contribution to respiratory rhythm generation changes during the transition from normoxia to hypoxia. During hypoxia, blockade of neurons with sodium-dependent bursting properties abolishes respiratory rhythm generation, while in normoxia respiratory rhythm generation only ceases upon pharmacological blockade of neurons with heterogeneous bursting properties. We propose that respiratory rhythm generation in normoxia depends on a heterogeneous population of pacemaker neurons, while during hypoxia the respiratory rhythm is driven by only one type of pacemaker.